The regulation of ovarian follicle maturation depends on endocrine and paracrine acting factors, including follicle stimulating hormone (FSH), inhibin, and activin. Activin and inhibin are members of the TGF-beta superfamily of peptide hormones/growth factors that regulate many cellular growth and differentiation processes. Activin and inhibin play a central role in the reproductive systems of animals through the endocrine regulation of FSH levels and paracrine actions in both the testis and the ovary. Diseases of follicle maturation arise when one or more of these factors or signaling receptors are mis-regulated or mutated. Thus, in order to further clarify the mechanisms by which activin and inhibin act to regulate pituitary and gonadal function, biophysical and structural studies of the receptor:ligand interactions will be undertaken. These studies will allow for evaluation of the potential specific defects in inhibin mutations associated with naturally occurring mutations and lay the foundation for the development of novel ligands with enhanced therapeutic properties. The combination of biophysical, structural, and functional studies proposed will provide broader insight into the mechanisms of specificity and signal transduction associated with the TGF-beta superfamily, with implications for understanding fundamental processes in reproductive, developmental, cancer, and immuno-biology.